• Dwi Endarti Faculty of Pharmacy, Gadjah Mada University
  • Arthorn Riewpaiboon Faculty of Pharmacy, Mahidol University


Objective: Externalities, could be positive or negative effects, occur in almost all daily life including vaccination activities. This paper aimed to presents
a literature review of the concept of vaccination externalities and its application in pharmacoeconomic/economic evaluation studies.
Methods: The literature review was conducted to achieve the study objectives. Searching of literature used MEDLINE electronic database by PubMed
interface as well as Google scholar search engine and employed a number of keywords.
Results: There are three most common types of vaccination externalities, namely: Herd immunity, serotype replacement, and antibiotic resistance.
Herd immunity gives positive effects to the benefit of vaccination, the opposite of that of serotype replacement; while antibiotic resistance could give
either positive or negative effects to the benefit of vaccination. Most emergence of serotype replacement occurred after pneumococcal conjugate
vaccine vaccination. Most of pharmacoeconomic studies of vaccination used dynamic models to capture vaccination externalities which often included
only herd immunity effects. Taking herd immunity into account in pharmacoeconomic studies tends to increase the outcomes and reduce the cost;
hence, the cost per outcome or incremental cost-effectiveness ratio will decrease, resulting more favorable cost-effectiveness ratio.
Conclusions: Vaccination externalities might have effect on the results of pharmacoeconomic studies. Attentiveness should be made to interpret the
results of pharmacoeconomic studies which potentially altered by the effect of vaccination externalities.
Keywords: Vaccination externality, Herd immunity, Serotype replacement, Antibiotic resistance, Pharmacoeconomic, Dynamic model.

Author Biographies

Dwi Endarti, Faculty of Pharmacy, Gadjah Mada University
Department of Pharmaceutics
Arthorn Riewpaiboon, Faculty of Pharmacy, Mahidol University
Department of Pharmacy


1. Carande-Kulis VG, Getzen TE, Thacker SB. Public goods and
externalities: A research agenda for public health economics. J Public
Health Manag Pract 2007;13(2):227-32.
2. WHO. WHO Guide for Standardization of Economic Evaluations of
Immunization Programmes. Geneva: World Health Organization; 2008.
3. Boulier BL, Datta TS, Goldfarb RS. Vaccination externalities. B E J
Econom Anal Policy 2007;7(1):Art.23.
4. Stephens DS. Vaccines for the unvaccinated: Protecting the herd.
J Infect Dis 2008;197(5):643-5.
5. Bärnighausen T, Bloom DE, Canning D, Friedman A, Levine OS,
O’Brien J, et al. Rethinking the benefits and costs of childhood
vaccination: The example of the Haemophilus influenzae type b
vaccine. Vaccine 2011;29(13):2371-80.
6. Hanage WP, Finkelstein JA, Huang SS, Pelton SI, Stevenson AE,
Kleinman K, et al. Evidence that pneumococcal serotype replacement
in Massachusetts following conjugate vaccination is now complete.
Epidemics 2010;2(2):80-4.
7. Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease
after pneumococcal vaccination. Lancet 2011;378(9807):1962-73.
8. John TJ, Samuel R. Herd immunity and herd effect: New insights and
definitions. Eur J Epidemiol 2000;16(7):601-6.
9. Kim TH, Johnstone J, Loeb M. Vaccine herd effect. Scand J Infect Dis
10. Cook J, Jeuland M, Maskery B, Lauria D, Sur D, Clemens J, et al. Using
private demand studies to calculate socially optimal vaccine subsidies
in developing countries. J Policy Anal Manage 2009;28(1):6-28.
11. Fine P, Eames K, Heymann DL. “Herd immunity”: A rough guide. Clin
Infect Dis 2011;52(7):911-6.
12. Brisson M, Edmunds WJ. Economic evaluation of vaccination programs:
The impact of herd-immunity. Med Decis Making 2003;23(1):76-82.
13. Bonds MH, Rohani P. Herd immunity acquired indirectly from
interactions between the ecology of infectious diseases, demography
and economics. J R Soc Interface 2010;7(44):541-7.
14. Lewin EB. A paradigm for the control of influenza. J Infect Dis
15. Brisson M, Edmunds WJ. Impact of model, methodological, and
parameter uncertainty in the economic analysis of vaccination
programs. Med Decis Making 2006;26(5):434-46.
16. Trotter CL, Edmunds WJ. Reassessing the cost-effectiveness of
meningococcal serogroup C conjugate (MCC) vaccines using
The indirect effect of vaccination on the non-vaccinated individuals (the herd
immunity effect) is greater than the direct effect on individuals vaccinated.
The impact of vaccination was efficient when employing a dynamic approach
and was not if using static approach
HPV (dynamic) The inclusion of herd immunity reduced the cost per QALY gained by 12-31%.
The cost per QALY gained was less sensitive to changes in parameter values
when herd immunity was included in the model
(dynamic and static)
Incorporating the effect of possible indirect protection had a moderate
impact on the cost-effectiveness ratio in all the countries; in some countries,
it improved the cost-effectiveness ratios to be nearly favorable
Kim et al., 2010 [37] Gambia PCV (static) Less immunity waning and serotype replacement as well as more herd
immunity will decrease the ICER (improve the cost-effectiveness favorability)
MCV: Meningococcal vaccine, HPV: Human papillomavirus vaccine, PCV: Pneumococcal vaccine
a transmission dynamic model. Med Decis Making 2006;26(1):
17. Hammitt LL, Bruden DL, Butler JC, Baggett HC, Hurlburt DA,
Reasonover A, et al. Indirect effect of conjugate vaccine on adult
carriage of Streptococcus pneumoniae: An explanation of trends in
invasive pneumococcal disease. J Infect Dis 2006;193(11):1487-94.
18. Hanna JN, Humphreys JL, Murphy DM. Invasive pneumococcal disease
in Indigenous people in north Queensland: An update, 2005-2007. Med
J Aust 2008;189(1):43-6.
19. Jackson LA, Janoff EN. Pneumococcal vaccination of elderly adults:
New paradigms for protection. Clin Infect Dis 2008;47(10):1328-38.
20. Ardanuy C, Tubau F, Pallares R, Calatayud L, Domínguez MA, Rolo D,
et al. Epidemiology of invasive pneumococcal disease among adult patients
in barcelona before and after pediatric 7-valent pneumococcal conjugate
vaccine introduction, 1997-2007. Clin Infect Dis 2009;48(1):57-64.
21. Roca A, Hill PC, Townend J, Egere U, Antonio M, Bojang A, et al.
Effects of community-wide vaccination with PCV-7 on pneumococcal
nasopharyngeal carriage in the Gambia: A cluster-randomized trial.
PLoS Med 2011;8(10):e1001107.
22. Ramsay ME, Andrews NJ, Trotter CL, Kaczmarski EB, Miller E. Herd
immunity from meningococcal serogroup C conjugate vaccination in
England: Database analysis. BMJ 2003;326(7385):365-6.
23. Emch M, Ali M, Park JK, Yunus M, Sack DA, Clemens JD. Relationship
between neighbourhood-level killed oral cholera vaccine coverage
and protective efficacy: Evidence for herd immunity. Int J Epidemiol
24. Clark HF, Lawley D, Mallette LA, DiNubile MJ, Hodinka RL. Decline
in cases of rotavirus gastroenteritis presenting to The Children’s
Hospital of Philadelphia after introduction of a pentavalent rotavirus
vaccine. Clin Vaccine Immunol 2009;16(3):382-6.
25. Pai R, Moore MR, Pilishvili T, Gertz RE, Whitney CG, Beall B. Active
Bacterial Core Surveillance Team. Postvaccine genetic structure of
Streptococcus pneumoniae serotype 19A from children in the United
States. J Infect Dis 2005;192(11):1988-95.
26. Cohen R, Levy C, Bonnet E, Thollot F, Boucherat M, Fritzell B, et al.
Risk factors for serotype 19A carriage after introduction of 7-valent
pneumococcal vaccination. BMC Infect Dis 2011;11:95.
27. Simões AS, Pereira L, Nunes S, Brito-Avô A, de Lencastre H,
Sá-Leão R. Clonal evolution leading to maintenance of antibiotic
resistance rates among colonizing Pneumococci in the PCV7 era in
Portugal. J Clin Microbiol 2011;49(8):2810-7.
28. Muñoz-Almagro C, Jordan I, Gene A, Latorre C, Garcia-Garcia JJ,
Pallares R. Emergence of invasive pneumococcal disease caused by
nonvaccine serotypes in the era of 7-valent conjugate vaccine. Clin
Infect Dis 2008;46(2):174-82.
29. McQue K. Wyeth files Prevnar-13 in US while GSK’s rival vaccine
gains EU approval. SCRIPT World Pharmaceutical News. Available
30. Karnezis TT, Smith A, Whittier S, Haddad J, Saiman L. Antimicrobial
resistance among isolates causing invasive pneumococcal disease
before and after licensure of heptavalent conjugate pneumococcal
vaccine. PLoS One 2009;4(6):e5965.
31. Kyaw MH, Lynfield R, Schaffner W, Craig AS, Hadler J, Reingold A,
Asian J Pharm Clin Res, Vol 9, Issue 1, 2016, 204-208
Endarti and Riewpaiboon
et al. Effect of introduction of the pneumococcal conjugate vaccine
on drug-resistant Streptococcus pneumoniae. N Engl J Med
32. Talbot TR, Poehling KA, Hartert TV, Arbogast PG, Halasa NB,
Mitchel E, et al. Reduction in high rates of antibiotic-nonsusceptible
invasive pneumococcal disease in after introduction of the
pneumococcal conjugate vaccine. Clin Infect Dis 2004;39(5):641-8.
33. Lopez E, Debbag R, Coudeville L, Baron-Papillon F, Armoni J. The
cost-effectiveness of universal vaccination of children against hepatitis
A in Argentina: Results of a dynamic health-economic analysis.
J Gastroenterol 2007;42(2):152-60.
34. Pradas-Velasco R, Antoñanzas-Villar F, Martínez-Zárate MP.
Dynamic modelling of infectious diseases: An application to the
economic evaluation of influenza vaccination. Pharmacoeconomics
35. Anonychuk AM, Bauch CT, Merid MF, Van Kriekinge G, Demarteau N.
A cost-utility analysis of cervical cancer vaccination in preadolescent
Canadian females. BMC Public Health 2009;9:401.
36. Jit M, Bilcke J, Mangen MJ, Salo H, Melliez H, Edmunds WJ, et al.
The cost-effectiveness of rotavirus vaccination: Comparative analyses
for five European countries and transferability in Europe. Vaccine
37. Kim SY, Lee G, Goldie SJ. Economic evaluation of pneumococcal
conjugate vaccination in The Gambia. BMC Infect Dis 2010;10:260.
298 Views | 530 Downloads
How to Cite
Endarti, D., and A. Riewpaiboon. “VACCINATION EXTERNALITIES: THE CONCEPT AND APPLICATION IN PHARMACOECONOMIC STUDIES”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 9, no. 1, Jan. 2016, pp. 204-8,
Original Article(s)